Influenza vaccines generally do not include an adjuvant, except for the PREPANDRIX™ product (GlaxoSmithKline) and the FLUAD™ product (Novartis Vaccines). The adjuvant in the monovalent pre-pandemic seasonal PREPANDRIX™ vaccine is an oil-in-water emulsion. The antigen and the emulsion adjuvant are supplied in separate 10-dose vials for mixing at the point of use at a 1:1 volume ratio. The product datasheet shows that each dose has a volume of 0.5 mL and contains 3.75 μg HA with 10.68 mg squalene and 4.85 mg polysorbate 80.
The adjuvant in the trivaient seasonal FLUAD™ vaccine is an oil-in-water emulsion. The antigen and the emulsion adjuvant are supplied in pre-mixed format in a pre-filled syringe. The product datasheet shows that each dose has a volume of 0.5 mL and contains 15 μg hemagglutinin (HA) per strain with 9.75 mg squalene and 1.175 mg polysorbate 80. As disclosed in reference 1, the vaccine is made by mixing at a 2× emulsion with a 2× antigen solution at a 1:1 volumetric ratio, to give a final solution with both emulsion and antigen at the 1× concentration. This 1:1 mixing ratio is further explained in chapter 10 of reference 75. Modifications of this mixing are disclosed in reference 2.
Compared to the FLUAD™ product, reference 3 discloses trivalent influenza vaccines with lower amounts of HA (3×5 μg HA/dose) and lower amounts of squalene (5.35 mg/dose). The vaccine includes thiomersal preservative and was administered to humans as a 0.5 mL dose.
It is an object of the invention to provide further and improved formulations of adjuvanted influenza vaccines, and in particular of seasonal influenza vaccines.